(1) Background: The safe performance of pharmacists is an important issue for patients and regulators. It is recognized that pharmacists interact with a variety of healthcare professionals and act as a bridge between other healthcare providers and systems and patients in the health setting. There has been growing activity in exploring factors that impact optimal performance and determinants that are linked with medication errors and practice incidents. The aviation and military industries have used S.H.E.L.L modeling to identify how personnel interact with factors that affect outcomes. A human factors approach is a useful angle to take when trying to improve optimal practice. Little is known about the experiences of New Zealand pharmacists and S.H.E.L.L factors that affect day-to-day practices in their work environment. (2) Methods: We investigated environment, team, and organizational considerations as the determining factors of optimal work practices using an anonymous online questionnaire. The questionnaire was built from a modified version of the software, hardware, environment, and liveware (S.H.E.L.L) model. This identified components of a work system that were vulnerable and that provided risks to optimal practice. Participants were New Zealand pharmacists approached through a subscriber list provided by the regulatory authority of the profession. (3) Results: We received responses from 260 participants (8.56%). The majority of participants indicated that optimal practice was occurring. More than 95% of respondents agreed that knowledge, fatigue interruptions, complacency, and stress affected optimal practice. Equipment and tools, medication arrangement on the shelf, lighting, physical layout, and communication with staff and patients were important factors for optimal practice. A smaller cohort of participants, 13 percent (n
= 21), stated that dispensing processes, dissemination, and enforcement of standard operating procedures and procedural guidance did not affect pharmacy practice, 21.3% responded that professional and ethical requirements did not affect optimal practice, 20% stated that having a staffroom affected optimal practice, 20% did not think substance use affected optimal practice, and 30% did not state that cultural differences affected optimal practice. Optimal practice is constrained when there is a lack of experience, professionalism, and communication among staff, patients, and external agencies. COVID-19 also has had an impact on pharmacists both personally and in their work environments. Exploring how the pandemic has affected pharmacists and their work environment warrants further research. (4) Conclusions: Pharmacists across New Zealand agreed that optimal practices were occurring and considered other factors that were perceived to not affect optimal practice. A human factor S.H.E.L.L framework has been used to analyze themes to understand the optimal practice. The rising body of international literature on the effect of the pandemic on pharmacy practice serves as a foundation for many of these themes. Longitudinal data would be useful in exploring some factors, such as pharmacist well-being over time.